title: HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.
abstract: BACKGROUND
  Human leucocyte antigens (HLAs) modulate immunity to polyomavirus BK (BKV). Identification of HLAs that alter the course of infection will facilitate risk stratification, and customization of pre-emptive intervention strategies.
  
  
  METHODS
  We performed a retrospective cohort study with 998 kidney transplant patients with BKV infection status confirmed by polymerase chain reaction (PCR). Clinical parameters and donor-recipient matching for specific HLAs were examined in relation to occurrence of viremia. An emphasis was placed on donor-recipient matching rather than the actual frequency of specific HLA-alleles, since a successful immune response requires sharing of HLAs between a virus-infected target cell and the anti-viral effector cell.
  
  
  RESULTS
  Using multivariate statistics, low risk of BK viremia was associated with matching of HLA-A2 [hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.28-0.85], HLA-B44 (HR 0.31, 95% CI 0.076-0.85) and HLA-DR15 (HR 0.35, 95% CI 0.084-0.93) (P < 0.05), whereas high risk of viremia was associated with male gender (HR 2.38, 95% CI 1.46-4.09, P < 0.001).
  
  
  CONCLUSIONS
  HLAs that associated with a lower predisposition to the development of BK viremia have been identified. Evaluation of donor-recipient mismatching for these HLAs could potentially be used to (i) fine tune virus screening strategies for BKV in individual patients and (ii) facilitate discovery of major histocompatibility complex (MHC) class I and II binding peptides that can elicit clinically meaningful BKV-specific immunity.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
mesh_terms: D000328:Adult; D064591:Allografts; D001739:BK Virus / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism*; D059948:HLA-B44 Antigen / Q000276:immunology / Q000378:metabolism*; D059810:HLA-DR Serological Subtypes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology / Q000628:therapy / Q000821:virology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014766:Viremia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D004279:DNA, Viral; D015789:HLA-A2 Antigen; D059948:HLA-B44 Antigen; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen
keywords: HLA mismatch; genotype; polymerase chain reaction (PCR); screening; viremia